Heart failure is the number one cause of morbidity and mortality in the U.S and an epidemic worldwide. The lack of transplantable hearts or effective drug/device to cure heart failure necessitates novel and out-of-the-box solution to address this growing challenge. Recent advances in engineering technology has brought forth mechanical devices such as left ventricular assist device and total artificial heart which provides short-term support of cardiac function. However, significant challenges remain for these devices to integrate naturally and survive long-term without thrombotic and infectious complications and foreign-body immune rejection. We believe there is a tremendous need to improve tissue-machine interface that can harmonizes synthetic material with the human tissue. The formulation of scientific principles that enable seamless integration between human tissue and its synthetic replacement could lead to the establishment of an entirely new field of research. In this proposal we plan to integrate three innovative developments in tissue engineering and stem cell biology. First, we will employ 3D printing to generate a wide variety of physiological shapes and structures including replacement tissues such as vascular conduit, heart valves, and ventricular assist device. Second, we will integrate human decellularized matrix into the 3D printer to generate biological scaffold in the shape of custom designed tissue. Third, we will incorporate specific cells types into the scaffold by seeding induced pluripotent stem cell (iPSC)-derived endothelial, smooth muscle, or mesenchymal cells and cardiomyocytes to generate replacement tissues of interest. By combining 3D printing, decellularized human matrix, and differentiated iPSCs we hope to create synthetic blood vessel, heart valve, or ventricular assist devices that are biologically compatible with the recipient tissue and minimize if not eliminate infectious, thrombotic, and immunological complications.